The aim of the HERITAGE Family Study is to document cardiovascular and metabolic responses to endurance exercise, and the contribution of genetic factors to the concomitant responses of cardiovascular disease (CVD) and diabetes (NIDDM) risk factors. A consortium of 5 universities is conducting the study. In Phase I (1992- 1997), about 765 sedentary subjects were exercise-trained with the same program for 20 weeks. There will be in the final master file about 495 individuals from 98 families of Caucasian descent with both parents and biological adult offspring and 270 individuals from 102 Black families. Before and after training, maximal oxygen uptake and cardiovascular and metabolic responses to submaximal and maximal exercise were measured. Plasma lipids, lipoproteins, apolipoproteins and enzymes related to lipid-metabolism, insulin and glucose response to an intravenous glucose load, plasma sex steroids and glucocorticoids, resting and exercise blood pressures, and body fat, regional fat distribution and visceral fat were assessed. During the proposed Phase 2, a series of nongenetic studies will be undertaken on the HERITAGE family dataset. Physiolocial, behavioral and social determinants of maximal and submaximal indicators of cardiorespiratory endurance in the sedentary state an din the response to training will be investigated, taking into account the contributions of age, gender and race. Similar analyses will be carried out on the CVD and NIDDM risk factors monitored in the study. Genetic analyses will determine the heritability levels, and test for paternal or maternal effects, major gene effects and segregation patterns which will be used to develop hypotheses concerning genetic bases of the response to endurance exercise. A panel of candidate genes will be typed and used for association and linkage studies. Differential display analyses of skeletal muscle transcripts will be used to identify new candidate genes for the response to endurance exercise. Finally, a genome wide search will be undertaken to locate candidate genomic regions and positional candidate genes for the response of cardiorespiratory endurance and CVD and NIDDM risk factor phenotypes. This phase of the HERITAGE Family Study should increase our understanding of the differences between Black and White for common CVD and NIDDM risk factors in the sedentary state and of the genetics of adaptation to regular endurance exercise in these risk factors with an emphasis on potential racial differences. This application is from the University of Minnesota Clinical Center.